tbuckley/cabot-search huggingface dataset:
One-step fabrication of cell sheet-laden hydrogel for accelerated wound healing
Authors: Huijuan Wang, Deshun Sun, Weiming Lin, Chao Fang, Kui Cheng, Zhengzhou Pan, Daping Wang, Zhangfa Song, Xiaojun Long
Journal: Bioactive Materials (2023)

Full-thickness skin wounds are have continued to be reconstructive challenges in dermal and skin appendage regeneration, and skin substitutes are promising tools for addressing these reconstructive procedures. Herein, the one-step fabrication of a cell sheet integrated with a biomimetic hydrogel as a tissue engineered skin for skin wound healing generated in one step is introduced. Briefly, cell sheets with rich extracellular matrix, high cell density, and good cell connections were integrated with biomimetic hydrogel to fabricate gel + human skin fibroblasts (HSFs) sheets and gel + human umbilical vein endothelial cells (HUVECs) sheets in one step for assembly as a cell sheet-laden hydrogel (CSH). The designed biomimetic hydrogel formed with UV crosslinking and ionic crosslinking exhibited unique properties due to the photo-generated aldehyde groups, which were suitable for integrating into the cell sheet, and ionic crosslinking reduced the adhesive force toward the substrate. These properties allowed the gel + cell sheet film to be easily released from the substrate. The cells in the harvested cell sheet maintained excellent viability, proliferation, and definite migration abilities inside the hydrogel. Moreover, the CSH was implanted into a full-thickness skin defects to construct a required dermal matrix and cell microenvironment. The wound closure rate reached 60.00 ± 6.26% on the 2nd day, accelerating mature granulation and dermis formation with skin appendages after 14 days. This project can provide distinct guidance and strategies for the complete repair and regeneration of full-thickness skin defects, and provides a material with great potential for tissue regeneration in clinical applications.
Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment
Authors: Eva S. Thomas, Henry L. Gomez, Rubi K. Li, Hyun-Cheol Chung, Luis E. Fein, Valorie F. Chan, Jacek Jassem, Xavier B. Pivot, Judith V. Klimovsky, Fernando Hurtado de Mendoza, Binghe Xu, Mario Campone, Guillermo L. Lerzo, Ronald A. Peck, Pralay Mukhopadhyay, Linda T. Vahdat, Henri H. Roché
Journal: Journal of Clinical Oncology (2007)

Purpose Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer. Patients and Methods Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m 2 intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m 2 orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m 2 on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review. Results Ixabepilone plus capecitabine prolonged progression-free survival relative to capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35% v 14%; P &lt; .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [≥ grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups. Conclusion Ixabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.
ASGCT 2023—Gene therapy is becoming medicine
Authors: Roland W. Herzog, Courtney Bricker-Anthony
Journal: Molecular Therapy (2023)

The 26th annual meeting of the American Society of Gene Therapy (ASGCT) took place in Los Angeles in May 2023. This year's meeting celebrated the precision that gene therapy has achieved, ranging from gene editing to specific targeting of cancer cells by receptor-engineered lymphocytes. Gene editing in particular took center stage this year during the Presidential Symposium. Jennifer Doudna explained the principle of gene editing using the CRISPR system and its applications in treatment of human diseases, while David Liu enlightened us on the ever-increasing precision of these evolving technologies and expansion of the toolkit to base and prime editors that do not require making DNA breaks. The strong interest in this area was also well reflected by the abstracts presented at the meeting. Gene editing and correction were among the top-performing abstract categories, accounting for 14% of all abstract submissions and 16% of all oral abstract presentations. Moreover, gene editing and correction are expanding into the clinic, as demonstrated by Haydar Frangoul, who focused on the highly promising outcomes of a clinical trial on gene editing for the treatment of transfusion-dependent β-thalassemia and severe sickle cell disease. Furthermore, J. Keith Joung received the society's Outstanding Achievement Award for his contributions to the development of nucleases for gene editing applications.
Lactation-associated macrophages exist in murine mammary tissue and human milk
Authors: Dilay Cansever, Ekaterina Petrova, Sinduya Krishnarajah, Caroline Mussak, Christina A. Welsh, Wiebke Mildenberger, Kevin Mulder, Victor Kreiner, Elsa Roussel, Sebastian A. Stifter, Myrto Andreadou, Pascale Zwicky, Nicole Puertas Jurado, Hubert Rehrauer, Ge Tan, Zhaoyuan Liu, Camille Blériot, Francesca Ronchi, Andrew J. Macpherson, Florent Ginhoux, Giancarlo Natalucci, Burkhard Becher, Melanie Greter
Journal: Nature Immunology (2023)

Abstract Macrophages are involved in immune defense, organogenesis and tissue homeostasis. Macrophages contribute to the different phases of mammary gland remodeling during development, pregnancy and involution postlactation. Less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multiparameter flow cytometry and single-cell RNA sequencing, we identified a lactation-induced CD11c + CX3CR1 + Dectin-1 + macrophage population (liMac) that was distinct from the two resident F4/80 hi and F4/80 lo macrophage subsets present pregestationally. LiMacs were predominantly monocyte-derived and expanded by proliferation in situ concomitant with nursing. LiMacs developed independently of IL-34, but required CSF-1 signaling and were partly microbiota-dependent. Locally, they resided adjacent to the basal cells of the alveoli and extravasated into the milk. We found several macrophage subsets in human milk that resembled liMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation.
Wnt signaling preserves progenitor cell multipotency during adipose tissue development
Authors: Zinger Yang Loureiro, Shannon Joyce, Tiffany DeSouza, Javier Solivan-Rivera, Anand Desai, Pantos Skritakis, Qin Yang, Rachel Ziegler, Denise Zhong, Tammy T. Nguyen, Ormond A. MacDougald, Silvia Corvera
Journal: Nature Metabolism (2023)

Abstract Mesenchymal stem/progenitor cells are essential for tissue development and repair throughout life, but how they are maintained under chronic differentiation pressure is not known. Using single-cell transcriptomics of human progenitor cells we find that adipose differentiation stimuli elicit two cellular trajectories: one toward mature adipocytes and another toward a pool of non-differentiated cells that maintain progenitor characteristics. These cells are induced by transient Wnt pathway activation and express numerous extracellular matrix genes and are therefore named structural Wnt-regulated adipose tissue cells. We find that the genetic signature of structural Wnt-regulated adipose tissue cells is present in adult human adipose tissue and adipose tissue developed from human progenitor cells in mice. Our results suggest a mechanism whereby adipose differentiation occurs concurrently with the maintenance of a mesenchymal progenitor cell pool, ensuring tissue development, repair and appropriate metabolic control over the lifetime.
Control and coding of pupil size by hypothalamic orexin neurons
Authors: Nikola Grujic, Alexander Tesmer, Ed Bracey, Daria Peleg-Raibstein, Denis Burdakov
Journal: Nature Neuroscience (2023)

Abstract Brain orexin (hypocretin) neurons are implicated in sleep–wake switching and reward-seeking but their roles in rapid arousal dynamics and reward perception are unclear. Here, cell-specific stimulation, deletion and in vivo recordings revealed strong correlative and causal links between pupil dilation—a quantitative arousal marker—and orexin cell activity. Coding of arousal and reward was distributed across orexin cells, indicating that they specialize in rapid, multiplexed communication of momentary arousal and reward states.
Transcriptomic classes of BCR-ABL1 lymphoblastic leukemia
Authors: Jaeseung C. Kim, Michelle Chan-Seng-Yue, Sabrina Ge, Andy G. X. Zeng, Karen Ng, Olga I. Gan, Laura Garcia-Prat, Eugenia Flores-Figueroa, Tristan Woo, Amy Xin Wei Zhang, Andrea Arruda, Shivapriya Chithambaram, Stephanie M. Dobson, Amanda Khoo, Shahbaz Khan, Narmin Ibrahimova, Ann George, Anne Tierens, Johann Hitzler, Thomas Kislinger, John E. Dick, John D. McPherson, Mark D. Minden, Faiyaz Notta
Journal: Nature Genetics (2023)

Abstract In BCR-ABL1 lymphoblastic leukemia, treatment heterogeneity to tyrosine kinase inhibitors (TKIs), especially in the absence of kinase domain mutations in BCR-ABL1 , is poorly understood. Through deep molecular profiling, we uncovered three transcriptomic subtypes of BCR-ABL1 lymphoblastic leukemia, each representing a maturation arrest at a stage of B-cell progenitor differentiation. An earlier arrest was associated with lineage promiscuity, treatment refractoriness and poor patient outcomes. A later arrest was associated with lineage fidelity, durable leukemia remissions and improved patient outcomes. Each maturation arrest was marked by specific genomic events that control different transition points in B-cell development. Interestingly, these events were absent in BCR-ABL1 + preleukemic stem cells isolated from patients regardless of subtype, which supports that transcriptomic phenotypes are determined downstream of the leukemia-initialing event. Overall, our data indicate that treatment response and TKI efficacy are unexpected outcomes of the differentiation stage at which this leukemia transforms.
A multimodal atlas of tumour metabolism reveals the architecture of gene–metabolite covariation
Authors: Elisa Benedetti, Eric Minwei Liu, Cerise Tang, Fengshen Kuo, Mustafa Buyukozkan, Tricia Park, Jinsung Park, Fabian Correa, A. Ari Hakimi, Andrew M. Intlekofer, Jan Krumsiek, Ed Reznik
Journal: Nature Metabolism (2023)

Tumour metabolism is controlled by coordinated changes in metabolite abundance and gene expression, but simultaneous quantification of metabolites and transcripts in primary tissue is rare. To overcome this limitation and to study gene-metabolite covariation in cancer, we assemble the Cancer Atlas of Metabolic Profiles of metabolomic and transcriptomic data from 988 tumour and control specimens spanning 11 cancer types in published and newly generated datasets. Meta-analysis of the Cancer Atlas of Metabolic Profiles reveals two classes of gene-metabolite covariation that transcend cancer types. The first corresponds to gene-metabolite pairs engaged in direct enzyme-substrate interactions, identifying putative genes controlling metabolite pool sizes. A second class of gene-metabolite covariation represents a small number of hub metabolites, including quinolinate and nicotinamide adenine dinucleotide, which correlate to many genes specifically expressed in immune cell populations. These results provide evidence that gene-metabolite covariation in cellularly heterogeneous tissue arises, in part, from both mechanistic interactions between genes and metabolites, and from remodelling of the bulk metabolome in specific immune microenvironments.
Adipogenic and SWAT cells separate from a common progenitor in human brown and white adipose depots
Authors: Nagendra P Palani, Carla Horvath, Pascal N Timshel, Pytrik Folkertsma, Alexander G B Grønning, Tora I Henriksen, Lone Peijs, Verena H Jensen, Wenfei Sun, Naja Z Jespersen, Christian Wolfrum, Tune H Pers, Søren Nielsen, Camilla Scheele
Journal: Nature Metabolism (2023)

Adipocyte function is a major determinant of metabolic disease, warranting investigations of regulating mechanisms. We show at single-cell resolution that progenitor cells from four human brown and white adipose depots separate into two main cell fates, an adipogenic and a structural branch, developing from a common progenitor. The adipogenic gene signature contains mitochondrial activity genes, and associates with genome-wide association study traits for fat distribution. Based on an extracellular matrix and developmental gene signature, we name the structural branch of cells structural Wnt-regulated adipose tissue-resident (SWAT) cells. When stripped from adipogenic cells, SWAT cells display a multipotent phenotype by reverting towards progenitor state or differentiating into new adipogenic cells, dependent on media. Label transfer algorithms recapitulate the cell types in human adipose tissue datasets. In conclusion, we provide a differentiation map of human adipocytes and define the multipotent SWAT cell, providing a new perspective on adipose tissue regulation.
Chimeric antigen receptor T cell-based targeting of CD317 as a novel immunotherapeutic strategy against glioblastoma
Authors: Lena Hänsch, Matthias Peipp, Maximilian Mastall, Danielle Villars, Renier Myburgh, Manuela Silginer, Tobias Weiss, Dorothee Gramatzki, Flavio Vasella, Markus G Manz, Michael Weller, Patrick Roth
Journal: Neuro-Oncology (2023)

Chimeric antigen receptor (CAR) T cell therapy has proven to be successful against hematological malignancies. However, exploiting CAR T cells to treat solid tumors is more challenging for various reasons including the lack of suitable target antigens. Here, we identify the transmembrane protein CD317 as a novel target antigen for CAR T cell therapy against glioblastoma, one of the most aggressive solid tumors.
Characterization of novel loci controlling seed oil content in Brassica napus by marker metabolite-based multi-omics analysis
Authors: Long Li, Zhitao Tian, Jie Chen, Zengdong Tan, Yuting Zhang, Hu Zhao, Xiaowei Wu, Xuan Yao, Weiwei Wen, Wei Chen, Liang Guo
Journal: Genome biology (2023)

Abstract Background Seed oil content is an important agronomic trait of Brassica napus ( B. napus ), and metabolites are considered as the bridge between genotype and phenotype for physical traits. Results Using a widely targeted metabolomics analysis in a natural population of 388 B. napus inbred lines, we quantify 2172 metabolites in mature seeds by liquid chromatography mass spectrometry, in which 131 marker metabolites are identified to be correlated with seed oil content. These metabolites are then selected for further metabolite genome-wide association study and metabolite transcriptome-wide association study. Combined with weighted correlation network analysis, we construct a triple relationship network, which includes 21,000 edges and 4384 nodes among metabolites, metabolite quantitative trait loci, genes, and co-expression modules. We validate the function of BnaA03.TT4, BnaC02.TT4, and BnaC05.UK, three candidate genes predicted by multi-omics analysis, which show significant impacts on seed oil content through regulating flavonoid metabolism in B. napus . Conclusions This study demonstrates the advantage of utilizing marker metabolites integrated with multi-omics analysis to dissect the genetic basis of agronomic traits in crops.
Purging and accumulation of genetic load in conservation
Authors: Nicolas Dussex, Hernán E. Morales, Christine Grossen, Love Dalén, Cock van Oosterhout
Journal: Trends in Ecology & Evolution (2023)

Our ability to assess the threat posed by the genetic load to small and declining populations has been greatly improved by advances in genome sequencing and computational approaches. Yet, considerable confusion remains around the definitions of the genetic load and its dynamics, and how they impact individual fitness and population viability. We illustrate how both selective purging and drift affect the distribution of deleterious mutations during population size decline and recovery. We show how this impacts the composition of the genetic load, and how this affects the extinction risk and recovery potential of populations. We propose a framework to examine load dynamics and advocate for the introduction of load estimates in the management of endangered populations.
Prerequisites of language acquisition in the newborn brain
Authors: Teija Kujala, Eino Partanen, Paula Virtala, István Winkler
Journal: Trends in Neurosciences (2023)

Learning to decode and produce speech is one of the most demanding tasks faced by infants. Nevertheless, infants typically utter their first words within a year, and phrases soon follow. Here we review cognitive abilities of newborn infants that promote language acquisition, focusing primarily on studies tapping neural activity. The results of these studies indicate that infants possess core adult auditory abilities already at birth, including statistical learning and rule extraction from variable speech input. Thus, the neonatal brain is ready to categorize sounds, detect word boundaries, learn words, and separate speech streams: in short, to acquire language quickly and efficiently from everyday linguistic input.
Author Correction: A symbolic Neanderthal accumulation of large herbivore crania
Authors: Enrique Baquedano, Juan L Arsuaga, Alfredo Pérez-González, César Laplana, Belén Márquez, Rosa Huguet, Sandra Gómez-Soler, Lucía Villaescusa, M Ángeles Galindo-Pellicena, Laura Rodríguez, Rebeca García-González, M-Cruz Ortega, David M Martín-Perea, Ana I Ortega, Lucía Hernández-Vivanco, Gonzalo Ruiz-Liso, Juan Gómez-Hernanz, José I Alonso-Martín, Ana Abrunhosa, Abel Moclán, Ana I Casado, Marina Vegara-Riquelme, Ana Álvarez-Fernández, Ángel C Domínguez-García, Diego J Álvarez-Lao, Nuria García, Paloma Sevilla, Hugues-Alexandre Blain, Blanca Ruiz-Zapata, M José Gil-García, Adrián Álvarez-Vena, Teresa Sanz, Rolf Quam, Tom Higham
Journal: Nature Human Behaviour (2023)
Enterosignatures define common bacterial guilds in the human gut microbiome
Authors: Clémence Frioux, Rebecca Ansorge, Ezgi Özkurt, Chabname Ghassemi Nedjad, Joachim Fritscher, Christopher Quince, Sebastian M. Waszak, Falk Hildebrand
Journal: Cell Host & Microbe (2023)

The human gut microbiome composition is generally in a stable dynamic equilibrium, but it can deteriorate into dysbiotic states detrimental to host health. To disentangle the inherent complexity and capture the ecological spectrum of microbiome variability, we used 5,230 gut metagenomes to characterize signatures of bacteria commonly co-occurring, termed enterosignatures (ESs). We find five generalizable ESs dominated by either Bacteroides, Firmicutes, Prevotella, Bifidobacterium, or Escherichia. This model confirms key ecological characteristics known from previous enterotype concepts, while enabling the detection of gradual shifts in community structures. Temporal analysis implies that the Bacteroides-associated ES is "core" in the resilience of westernized gut microbiomes, while combinations with other ESs often complement the functional spectrum. The model reliably detects atypical gut microbiomes correlated with adverse host health conditions and/or the presence of pathobionts. ESs provide an interpretable and generic model that enables an intuitive characterization of gut microbiome composition in health and disease.
The role of cellular and molecular neuroimmune crosstalk in gut immunity
Authors: Daping Yang, Nicole Almanzar, Isaac M. Chiu
Journal: Cellular and Molecular Immunology (2023)

Abstract The gastrointestinal tract is densely innervated by the peripheral nervous system and populated by the immune system. These two systems critically coordinate the sensations of and adaptations to dietary, microbial, and damaging stimuli from the external and internal microenvironment during tissue homeostasis and inflammation. The brain receives and integrates ascending sensory signals from the gut and transduces descending signals back to the gut via autonomic neurons. Neurons regulate intestinal immune responses through the action of local axon reflexes or through neuronal circuits via the gut-brain axis. This neuroimmune crosstalk is critical for gut homeostatic maintenance and disease resolution. In this review, we discuss the roles of distinct types of gut-innervating neurons in the modulation of intestinal mucosal immunity. We will focus on the molecular mechanisms governing how different immune cells respond to neural signals in host defense and inflammation. We also discuss the therapeutic potential of strategies targeting neuroimmune crosstalk for intestinal diseases.
The Bovine Pangenome Consortium: democratizing production and accessibility of genome assemblies for global cattle breeds and other bovine species
Authors: Timothy P L Smith, Derek M Bickhart, Didier Boichard, Amanda J Chamberlain, Appolinaire Djikeng, Yu Jiang, Wai Y Low, Hubert Pausch, Sebastian Demyda-Peyrás, James Prendergast, Robert D Schnabel, Benjamin D Rosen
Journal: Genome biology (2023)

Abstract The Bovine Pangenome Consortium (BPC) is an international collaboration dedicated to the assembly of cattle genomes to develop a more complete representation of cattle genomic diversity. The goal of the BPC is to provide genome assemblies and a community-agreed pangenome representation to replace breed-specific reference assemblies for cattle genomics. The BPC invites partners sharing our vision to participate in the production of these assemblies and the development of a common, community-approved, pangenome reference as a public resource for the research community ( https://bovinepangenome.github.io/ ). This community-driven resource will provide the context for comparison between studies and the future foundation for cattle genomic selection.